ARX517 in Subjects With Advanced Solid Tumor (ARX517)

N
Nabil Adra, MD

Primary Investigator

Overview

A Phase 1, Multicenter, Open-label, Dose-escalation, and Dose expansion Study to Evaluate they, Pharmacokinetics, and Anti-tumor Activity of ARX517 in Subjects with Advanced Solid Tumor with known PSMA Who Failed Prior Standard Therapies

Description

This is a first-in-human, Phase 1, multicenter, open-label, single arm, dose escalation, and dose expansion study to evaluate the safety, PK, and preliminary anti-tumor activity of ARX517 in adult subjects with advanced solid tumor who failed prior standard therapies. Theudy includes 2 parts: a dose-escalation part (Part 1) and a dose-expansion part (Part 2).Part 1, the subject will be enrolled with a starting dose of 0.32 mg/kg, and the study will evaluate up to 6 dose levels of ARX517 (0.32 mg/kg, 0.64 mg/kg, 1.07 mg/kg, 1.4 mg/kg, 1.7 mg/kg, and 2.0 mg/kg) by intravenous infusion once every 3 weeks (Q3W). If the planned highest dose level of 2.0 mg/kg is well tolerated, a higher dose level of ARX517 may bevaluated based on the SMC recommendation. Similarly, doses lower than the pre-specifiedwest dose of 0.32 mg/kg and additional intermediate dose levels of ARX517 may also bedered if needed. Decisions about enrollment suspension, resumption, and studywill be made by the Sponsor based on recommendations from SMC. DLT will bevaluated in the first cycle of 21 days for Q3W. MTD and /or putative recommended phase II dose (RP2D) will be selected based on all available safety, tolerability, PK, and primaryumor activity data. To ensure that the selected RP2D is not associated with and risk of serious adverse events, multiple "putative RP2D" doses may be selected forurther evaluation based on SMC recommendation. The number of subjects to be enrolled in the dose-expansion part will be based on the number of doses selected for expansion and theults of the dose escalation part. Part 2 will not exceed 40 subjects.

Eligibility

You may be eligible for this study if you meet the following criteria:

  • Conditions:
    Advanced Solid Tumor, Solid Neoplasm
  • Age: 18 Years
  • Gender: All

Inclusion Criteria:
  1. Male subjects ≥18 years at the time of providing written informed consent
  2. Pathologically confirmed adenocarcinoma of the prostate or other solid tumors
  3. For prostate cancer, ongoing therapy with a gonadotropin-releasing hormone agonist orgonist AND serum testosterone level <50 ng/dL at Screening
  4. For prostate cancer, prior treatment with at least 2 Food and Drug Administration(FDA) approved treatments for metastatic castration-resistant prostate cancer.
  5. Metastatic disease documented by computed tomography (CT)/ magnetic resonance imaging(MRI) and/ or bone scan; images obtained within 28 days prior to the start of studydication will be accepted as baseline
  6. For prostate cancer, meet the criteria of disease progression according to thedations of the Prostate Cancer Working Group (PCWG) 3 by one of the following
    1. A sequential rise of PSA (second value obtained at a minimum of 1 week later)baseline measurement of at least 2 ng/mL (1 ng/mL is the minimum startingvalue if confirmed rise is only indication of progression)
    2. Radiographic progression (CT/MRI) by Response Evaluation Criteria in Solid Tumors(RECIST v 1.1) criteria
    3. Nuclear scan progression by new lesions
  7. For prostate cancer, discontinuation of flutamide or nilutamide, and other non
    steroidal anti-androgens at least 4 weeks prior to the start of study drug;discontinuation of bicalutamide at least 6 weeks prior to start of study drug.
  8. Discontinuation of radiotherapy >4 weeks prior
  9. Eastern Cooperative Oncology Group performance status of 0 to 1 at Screening
  10. Adequate organ function with following blood counts at Screening:
  11. Adequate organ function with following Chemistry values at Screening:
  12. Life expectancy of at least 6 months at Screening as per Investigator's judgment
  13. Willing and able to provide written informed consent for participation in the study,d comply with all protocol requirements and assessments
  14. Agrees to use contraception during the Treatment Period plus an additional 120 dayshe last dose of study treatment and must refrain from donating sperm duringhis period.
Exclusion Criteria:
  1. History of allergic reactions to any component of the ARX517.
  2. Impaired pituitary or adrenal gland function (e.g., Addison's disease, Cushing'syndrome)
  3. Initiation of bisphosphonate or denosumab therapy within 30 days prior to the start ofudy medication; subjects who are on a stable dose of these medications for at least30 days at the time of starting study drug are eligible
  4. Therapy with estrogen within 30 days prior to the start of study drug
  5. Use of systemic glucocorticoids equivalent to >10 mg prednisone daily; subjects whohave discontinued or are on reduced daily dose are eligible within 14 days prior tohe start of study drug
  6. Use of any medication such as finasteride/dutasteride known to decrease PSA levels(e.g., saw palmetto) within 30 days of start of study drug
  7. Have central nervous system (CNS) metastasis, unless the CNS metastasis was treatedwith local therapy and has proven to be stable over the last 2 months prior tog, and not currently requiring ongoing systemic steroid treatment
  8. History of other malignancy within the previous 2 years (no longer being activelyd), except basal cell carcinoma
  9. Marked baseline prolongation of QT/QTc interval, e.g. repeated demonstrated of a QTcval > 480 milliseconds (ms) (CTCAE grade 1) using Fridericia's QT correctionula. Major surgery within 30 days prior to the start of study drug
  10. Blood transfusion within 30 days of Screening
  11. Serious and /or persistent infection within 14 days of the start of study drug
  12. Treatment with any investigational drug within 4 weeks prior to Day 1 of the study
  13. Known seropositive test for human immunodeficiency virus or seropositive test forhepatitis C virus or hepatitis B virus (testing for hepatitis C and hepatitis B is notquired)
  14. Prior history of clinically significant lung disease, pneumonitis, or other clinicallygnificant lung disease within 12 months prior to Screening, with the exception ofhat directly attributable to the presence of lung metastases from their underlying.
  15. Prior history of clinically significant ocular events, or any current ongoing activeular infections.
  16. Major surgery within 30 days prior to the start of the study drug. Poorly controlleddiabetes, hypertension, history of class III or IV heart failure.

Updated on 29 Apr 2024. Study ID: ARX517-2011
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